Magnetic Resonance Imaging (MRI) is a non-invasive technique with broad diagnostic value. The technique has gained wide clinical acceptance and is of great importance in diagnostic medicine. However, despite significant technological advancements (increasing field strength and improvement in technology), applications of MRI are limited by an intrinsically low sensitivity.
Some alternatives to enhance its sensitivity have been developed which involve ex-vivo nuclear spin polarisation of agents, prior to administration and subsequent in-vivo measurement of the Magnetic Resonance (MR) signal as disclosed, for instance, in WO 98/01766, WO 98/58272 and WO 99/35508.
In particular, the process of Dynamic Nuclear Polarization (DNP) involves the preparation of a mixture comprising a hyperpolarizable molecule (typically enriched in a non-zero nuclear spin atom, e.g. 13C) together with a polarizing agent (e.g. a trityl radical). The sample is then frozen at very low temperatures (few ° K) for the polarization process. As successful polarization levels are generally achieved when the mixture upon freezing forms a glass (rather than a crystallized sample), the mixture may thus further comprise a glass-forming agent (e.g. glycerol, DMSO, etc.) to avoid crystallization of the sample.
Once the desired level of polarization is achieved, the sample is rapidly dissolved in an aqueous carrier and administered to a patient, for subsequent MR signal detection. Before administration of the hyperpolarized sample, the polarizing agent (in particular the trityl radical) is preferably removed, at least in part, from the mixture.
The Applicant has however observed that the trityl radicals generally employed in the art are relatively soluble in the aqueous preparation for the administration of the sample, which may render their separation from the mixture relatively cumbersome and/or only partial.
The Applicant has now found new trityl radicals which are substantially insoluble in water, thus allowing an effective separation of the radical from a hyperpolarized sample.